We discuss the limits of ground-based astrometry with adaptive optics based on experiments using the core of the Galactic globular cluster M5. We have recently achieved ⪅ 100microarcsecond astrometric precision and accuracy at the Hale 200-inch telescope. Here we apply the same experimental design considerations and optimal estimation technique to explore the astrometric precision of the Keck II telescope. We find that high-precision astrometry at ≈ 50 microarcsecond level is possible at Keck in 20 seconds. We discuss the potential of differential astrometry for current and next generation large aperture telescopes based on these results.© (2008) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.